Durhamycin A, a Potent Inhibitor of HIV Tat Transactivation
| Autor: | Lucia Herranz, Joanne E. Tomassini, Pia L. Graham, Donette S. Quamina, Deborah L. Zink, Russell B. Lingham, Ziqiang Guan, Magda M. Gagliardi, Renee Danzeisen, Sheo B. Singh, Hiranthi Jayasuriya, Olga Genilloud |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Costa Rica
Gene Expression Regulation Viral Magnetic Resonance Spectroscopy Anti-HIV Agents Stereochemistry Pharmaceutical Science Mass Spectrometry Substrate Specificity Analytical Chemistry Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Transactivation Drug Discovery Structure–activity relationship Tetrasaccharide Pharmacology Natural product Molecular Structure biology Hydrolysis Organic Chemistry Biological activity Plicamycin biology.organism_classification Aglycone Complementary and alternative medicine chemistry Viral replication Biochemistry Drug Design Gene Products tat Lentivirus HIV-1 Molecular Medicine tat Gene Products Human Immunodeficiency Virus Protein Binding |
| Zdroj: | Journal of Natural Products. 65:1091-1095 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/np010642f |
| Popis: | Tat is a small HIV protein essential for both viral replication and the progression of HIV disease. In our efforts to discover Tat inhibitors from natural product screening of microbial fermentation extracts, we discovered durhamycin A (1) as a potent inhibitor (IC(50) = 4.8 nM) of Tat transactivation. Detailed NMR and MS/MS studies were utilized to elucidate the structure of 1 as a new member of the aureolic acid family of antibiotics. It consists of tetrasaccharide and disaccharide moieties attached to the aglycone, which is hitherto unknown in the aureolic acid family. Three other novel analogues, durhamycin B (2), compound (3), and the aglycone (4), were also discovered or chemically prepared that were less potent than durhamycin A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|